Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia.
Pierre K BoerkoelKatherine DixonCarrie FitzsimonsYaoqing ShenStephanie HuynhKamilla Schlade-BartusiakLuka CulibrkSimon ChanElizabeth M J LeeSteven J M JonesHui-Lin ChinPublished in: American journal of medical genetics. Part A (2022)
Microphthalmia, anophthalmia, and coloboma (MAC) are a heterogeneous spectrum of anomalous eye development and degeneration with genetic and environmental etiologies. Structural and copy number variants of chromosome 13 have been implicated in MAC; however, the specific loci involved in disease pathogenesis have not been well-defined. Herein we report a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP) and terminal deletion. Sequence features at the breakpoint junctions suggested microhomology-mediated break-induced replication (MMBIR) of the maternal chromosome as the origin. Comparing this rearrangement to previously reported copy number alterations in 13q, we refine a putative dosage-sensitive critical region for MAC that might provide new insights into its molecular etiology.
Keyphrases
- copy number
- genome wide
- single molecule
- mitochondrial dna
- dna methylation
- intellectual disability
- single cell
- diabetic rats
- autism spectrum disorder
- magnetic resonance imaging
- drug induced
- oxidative stress
- body mass index
- climate change
- preterm birth
- genome wide association study
- risk assessment
- endothelial cells
- contrast enhanced
- computed tomography
- life cycle